TY - JOUR
T1 - Hematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation
AU - Ninni, Sandro
AU - Dombrowicz, David
AU - Kuznetsova, Tanya
AU - Vicario, Rocio
AU - Gao, Vance
AU - Molendi-Coste, Olivier
AU - Haas, Joel
AU - Woitrain, Eloise
AU - Coisne, Augustin
AU - Neele, Annette E
AU - Prange, Koen
AU - Willemsen, Lisa
AU - Aghezzaf, Samy
AU - Fragkogianni, Stamatina
AU - Tazibet, Amine
AU - Pineau, Laurent
AU - White, James Robert
AU - Eeckhoute, Jérôme
AU - Koussa, Mohamed
AU - Dubrulle, Henri
AU - Juthier, Francis
AU - Soquet, Jérôme
AU - Vincentelli, André
AU - Edme, Jean-Louis
AU - de Winther, Menno
AU - Geissmann, Frederic
AU - Staels, Bart
AU - Montaigne, David
N1 - Funding Information: The authors thank Bertrand Accart and the Biological Resources Center of Centre Hospitalier de Lille (BB 0033-00030) for handling and providing biological samples from the POMI-AF study. Publisher Copyright: © 2023 American College of Cardiology Foundation
PY - 2023/4/4
Y1 - 2023/4/4
N2 - BACKGROUND: On-pump cardiac surgery triggers sterile inflammation and postoperative complications such as postoperative atrial fibrillation (POAF). Hematopoietic somatic mosaicism (HSM) is a recently identified risk factor for cardiovascular diseases and results in a shift toward a chronic proinflammatory monocyte transcriptome and phenotype.OBJECTIVES: The aim of this study was to assess the prevalence, characteristics, and impact of HSM on preoperative blood and myocardial myeloid cells as well as on outcomes after cardiac surgery.METHODS: Blood DNA from 104 patients referred for surgical aortic valve replacement (AVR) was genotyped using the HemePACT panel (576 genes). Four screening methods were applied to assess HSM, and postoperative outcomes were explored. In-depth blood and myocardial leukocyte phenotyping was performed in selected patients using mass cytometry and preoperative and postoperative RNA sequencing analysis of classical monocytes.RESULTS: The prevalence of HSM in the patient cohort ranged from 29%, when considering the conventional HSM panel (97 genes) with variant allelic frequencies ≥2%, to 60% when considering the full HemePACT panel and variant allelic frequencies ≥1%. Three of 4 explored HSM definitions were significantly associated with higher risk for POAF. On the basis of the most inclusive definition, HSM carriers exhibited a 3.5-fold higher risk for POAF (age-adjusted OR: 3.5; 95% CI: 1.52-8.03; P = 0.003) and an exaggerated inflammatory response following AVR. HSM carriers presented higher levels of activated CD64 +CD14 +CD16 - circulating monocytes and inflammatory monocyte-derived macrophages in presurgery myocardium. CONCLUSIONS: HSM is frequent in candidates for AVR, is associated with an enrichment of proinflammatory cardiac monocyte-derived macrophages, and predisposes to a higher incidence of POAF. HSM assessment may be useful in the personalized management of patients in the perioperative period. (Post-Operative Myocardial Incident & Atrial Fibrillation [POMI-AF]; NCT03376165).
AB - BACKGROUND: On-pump cardiac surgery triggers sterile inflammation and postoperative complications such as postoperative atrial fibrillation (POAF). Hematopoietic somatic mosaicism (HSM) is a recently identified risk factor for cardiovascular diseases and results in a shift toward a chronic proinflammatory monocyte transcriptome and phenotype.OBJECTIVES: The aim of this study was to assess the prevalence, characteristics, and impact of HSM on preoperative blood and myocardial myeloid cells as well as on outcomes after cardiac surgery.METHODS: Blood DNA from 104 patients referred for surgical aortic valve replacement (AVR) was genotyped using the HemePACT panel (576 genes). Four screening methods were applied to assess HSM, and postoperative outcomes were explored. In-depth blood and myocardial leukocyte phenotyping was performed in selected patients using mass cytometry and preoperative and postoperative RNA sequencing analysis of classical monocytes.RESULTS: The prevalence of HSM in the patient cohort ranged from 29%, when considering the conventional HSM panel (97 genes) with variant allelic frequencies ≥2%, to 60% when considering the full HemePACT panel and variant allelic frequencies ≥1%. Three of 4 explored HSM definitions were significantly associated with higher risk for POAF. On the basis of the most inclusive definition, HSM carriers exhibited a 3.5-fold higher risk for POAF (age-adjusted OR: 3.5; 95% CI: 1.52-8.03; P = 0.003) and an exaggerated inflammatory response following AVR. HSM carriers presented higher levels of activated CD64 +CD14 +CD16 - circulating monocytes and inflammatory monocyte-derived macrophages in presurgery myocardium. CONCLUSIONS: HSM is frequent in candidates for AVR, is associated with an enrichment of proinflammatory cardiac monocyte-derived macrophages, and predisposes to a higher incidence of POAF. HSM assessment may be useful in the personalized management of patients in the perioperative period. (Post-Operative Myocardial Incident & Atrial Fibrillation [POMI-AF]; NCT03376165).
KW - Aortic Valve/surgery
KW - Atrial Fibrillation/etiology
KW - Cardiac Surgical Procedures/adverse effects
KW - Humans
KW - Mosaicism
KW - Postoperative Complications/epidemiology
KW - Risk Factors
UR - http://www.scopus.com/inward/record.url?scp=85150030998&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jacc.2023.01.036
DO - https://doi.org/10.1016/j.jacc.2023.01.036
M3 - Article
C2 - 36990546
SN - 0735-1097
VL - 81
SP - 1263
EP - 1278
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 13
ER -